The Zucker Diabetic Fatty Rat (ZDF) is a well accepted model of human obesity and non-insulin dependent diabetes mellitus (NIDDM). Animals inheriting the recessive (fa/fa) genotype develop early obesity, insulin resistance and, in males, a diabetic syndrome. Until the just reported (5/96) cloning of the fa gene, no adequate method existed for the early identification of pre-obese, pre-diabetic ZDF rats. We have recently demonstrated using the 4.7T system, that spectral analysis of fat content is highly sensitive and specific in detecting the pre-obese (fa/fa) genotype as early as 12 days of age, i.e. before gross obesity and associated metabolic derangements have developed. We are currently using this technique in intervention studies attempting to attenuate and/or prevent the obesity/diabetes syndrome. In addition, spectral analysis was validated using direct measurement of tissue water and lipid content and found to be highly correlated. This has allowed us to monitor the accretion of body fat non-invasively in vivo. We have also applied this technique to measuring regional body fat content in humans using our clinical 1.5T system. We are currently interested in the relationship between body fat content (as measured by spectral analysis), muscle triglyceride content and indices of insulin sensitivity and glucose tolerance. We have hypothesized that increases in muscle triglyceride content precedes major changes in body fat composition and may be an etiologic factor in the development of insulin resistance in human as well as rodent obesity and predispose to NIDDM. Studies are currently underway to test this hypothesis in our colony of ZDF rats, experimental dog models of fatty infiltration of muscle, as well as in human obesity and NIDDM.